CN112691238A

CN112691238A - Material with biological anti-fouling function, preparation method and application thereof

Info

Publication number: CN112691238A
Application number: CN202110060862.3A
Authority: CN
Inventors: 黄楠; 杨作霞; 钟永英
Original assignee: Chengdu Dingfeng Forward Looking Technology Co ltd
Current assignee: Chengdu Dingfeng Forward Looking Technology Co ltd
Priority date: 2021-01-18
Filing date: 2021-01-18
Publication date: 2021-04-23

Abstract

The invention discloses a material with a biological anti-fouling function, a preparation method and application thereof, and relates to the technical field of biological materials. The material with the biological anti-fouling function comprises a base material, a polyamine-phenol coating and a hyaluronic acid layer; wherein the polyamine-phenol coating is obtained by the reaction of phenolic molecules and polyamine molecules. The preparation method comprises the steps of forming a polyamine-phenol adhesive coating on a base material by utilizing a phenol amine chemical coating technology, and then covalently grafting hyaluronic acid by utilizing amine groups on the polyamine-phenol coating to form the hyaluronic acid coating. When the coating is contacted with aqueous solution, a hydration layer is formed on the surface to form a super-hydrophilic surface, so that the adhesion, migration and proliferation of components in blood, endothelial cells, smooth muscle cells, inflammatory cells and the like and coating modification materials are effectively inhibited, and the materials with the biological anti-fouling function, such as an inferior vena cava filter, an artificial heart inner wall anticoagulation surface, an artificial heart-lung machine anticoagulation surface and the like, can be prepared.

Description

Material with biological anti-fouling function, preparation method and application thereof

Technical Field

The invention relates to the technical field of biological materials, in particular to an anticoagulant and biological anti-fouling material, a preparation method and application thereof.

Background

Pulmonary artery embolism is a disease with high clinical mortality, although the prior systemic anticoagulation therapy can achieve certain curative effect, the occurrence of pulmonary artery embolism still cannot be completely avoided, the systemic anticoagulation therapy also has complications, and some patients cannot receive the systemic anticoagulation therapy. The inferior vena cava filter has been widely used in the world as a preventive measure for pulmonary artery embolism, and with the wide clinical use, some corresponding complications occur, so that the filter treatment fails and even the patient dies.

Because inferior vena cava filter is at implantation in-process, the operation can cause the damage to the vascular wall, and the damage of vascular wall can lead to the excessive hyperplasia of intima for filter and blood vessel adhesion, and then the vascular stenosis blocks up. In systemic anticoagulation treatment, contact of the filter with the vessel wall and blood will still to some extent, together with the intercepted thrombus, further activate to form a new thrombus, block the vessel or again cause pulmonary artery embolism. The above complications increase the risk of permanent filter failure, while with recyclable inferior vena cava filters, intimal coverage causes the filter to adhere to the blood vessel, making the filter recovery window smaller and recovery more difficult, as well as increasing the risk of surgical failure.

Therefore, the existing inferior vena cava filter has the problems of poor blood compatibility, difficult and even non-recoverable filter recovery caused by the fact that the existing inferior vena cava filter cannot effectively inhibit cell adhesion proliferation to form an inner membrane tissue, and the problems restrict the application of the inferior vena cava filter to a certain extent.

Disclosure of Invention

The invention aims to provide a material with a biological anti-fouling function, which aims to enable the material to have the performance of preventing cell adhesion by an anticoagulant and effectively inhibit complications caused by thrombosis and cell adhesion proliferation.

The invention also aims to provide a preparation method of the material with the biological anti-fouling function, the method is simple and easy to implement, and the prepared functional material has good anti-fouling performance.

The third purpose of the invention is to provide the application of the functional material in the preparation of inferior vena cava filters, artificial heart inner wall anticoagulation surfaces, artificial heart-lung machines anticoagulation surfaces and the like.

The technical problem to be solved by the invention is realized by adopting the following technical scheme.

The invention provides a material with a biological anti-fouling function, which comprises a substrate, a polyamine-phenol coating formed on the substrate and a hyaluronic acid layer formed on the polyamine-phenol coating; wherein the polyamine-phenol coating is obtained by the reaction of phenolic molecules and polyamine molecules, and the phenolic molecules are catechol or plant polyphenol.

The invention also provides a preparation method of the material with the biological anti-fouling function, which comprises the following steps:

reacting the substrate on which the phenolic molecule coating layer is deposited with a polyamine molecule solution to form a polyamine-phenolic coating layer on the substrate; grafting hyaluronic acid on the polyamine-phenolic coating.

The invention also provides application of the functional material in preparation of an inferior vena cava filter.

The invention also provides the application of the functional material in the preparation of the anticoagulation surface of the inner wall of the artificial heart.

The invention also provides the application of the functional material in the preparation of the anticoagulation surface of the artificial heart-lung machine.

The embodiment of the invention provides a material with a biological anti-fouling function, which has the following beneficial effects: the super-hydrophilic coating can effectively inhibit components, cells and the like in blood from contacting with the coating, thereby improving the blood compatibility of the material and effectively reducing the adhesion and proliferation of the cells on the material.

The embodiment of the invention also provides a preparation method of the material with the biological anti-fouling function, which comprises the steps of reacting the base material deposited with the phenolic molecule coating with the polyamine molecule solution to form the polyamine-phenolic coating on the base material, and then covalently grafting hyaluronic acid with carboxyl as a terminal group by using amine on the polyamine-phenolic coating to form a hyaluronic acid layer. When the coating is contacted with the aqueous solution, a hydration layer is formed on the surface, so that the contact of components, cells and the like in blood with the coating material is effectively inhibited, the prepared material has good blood compatibility, the adhesion and proliferation of the cells on the material can be effectively inhibited, the inferior vena cava filter with a recoverable function can be prepared, and the risks caused by operation failure and complications are obviously reduced. The functional material can also be used for preparing an anticoagulant surface on the inner wall of an artificial heart and an anticoagulant surface of an artificial heart-lung machine.

Drawings

In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.

FIG. 1 is a schematic diagram of a method for preparing a material with a biological anti-fouling function according to an embodiment of the present invention;

FIG. 2 shows contact angles before and after grafting of hyaluronic acid;

FIG. 3 is scanning electron microscope images of surface platelets before and after grafting of hyaluronic acid and fluorescence images of endothelial cells, smooth muscle cells and macrophages.

Detailed Description

In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.

The material with the biological anti-fouling function provided by the embodiment of the invention, the preparation method and the application thereof are specifically explained below.

The embodiment of the invention also provides a preparation method of the material with the biological anti-fouling function, and please refer to fig. 1, the preparation method comprises the following steps:

s1 formation of polyamine-phenol coating

The substrate deposited with the polydopamine coating is reacted with the polyamine molecular solution to form a polyamine-phenol coating on the substrate, and the polyamine-phenol coating formed by the reaction contains a large number of amine groups, thereby facilitating the introduction of other functional coatings.

Specifically, the process for preparing a substrate having a polyamine-phenolic coating deposited thereon comprises: soaking the substrate in a mixed solution of catechol monomer and tris buffer solution, and reacting for 1-24 h. The polyamine-phenolic coating is prepared by polymerizing catechol monomer in TRIS (hydroxymethyl) aminomethane (TRIS) buffer (controlling the pH of the solution to 7-10, such as 7, 8, 8.5, 9, or 10) to form a polyamine-phenolic coating on the surface of the substrate.

Specifically, the phenolic molecule is at least one selected from catechol, pyrogallol, epicatechin gallate, epigallocatechin gallate, dopamine, norepinephrine, levodopa, dextrodopa, gallic acid and its derivatives, tannic acid, caffeic acid, ferulic acid, 2, 3-dihydroxybenzoic acid and 3, 4-dihydroxybenzoic acid; preferably, the phenolic molecules are dopamine and norepinephrine. The polyamine molecules are selected from at least one of polyallylamine, polyvinylamine, polylysine and chitosan; preferably, the polyamine-based molecule is polyallylamine.

In some embodiments, the catechol is dopamine and the dopamine is present in an amount of 0.5-2mg/mL to form a uniform polydopamine coating on the substrate surface.

Further, the reaction of the base material deposited with the polydopamine coating and the polyamine molecular solution is to soak the base material deposited with the polydopamine coating in the polyamine molecular solution for 0.1 to 24 hours, preferably 4 to 8 hours; the polyamine molecular solution is a mixed solution of polyallylamine, strong base and solvent, and the pH value of the polyamine molecular solution is greater than 7, preferably 11-14. Under the strong alkali condition, the polydopamine coating is damaged and dissociated to promote the reaction of the polydopamine coating and primary amine groups on polyamine molecules, so that the coating is not disintegrated and is chemically re-crosslinked with polyallylamine to form the polydopamine conversion coating rich in amine groups.

Further, the concentration of the polyallylamine in the polyamine molecular solution is 0.1-50 mug/mL, preferably 2.5-20 mug/mL; the molecular weight of the polyallylamine is 1000-1000000; the strong base is sodium hydroxide, and the concentration of the sodium hydroxide in the polyamine molecular solution is 0.1-10mg/mL, preferably 2-3 mg/mL. By further controlling reaction parameters, the reaction of the polydopamine coating and the polyallylamine is promoted, more amine groups are introduced, and the subsequent grafting introduction of hyaluronic acid is facilitated.

S2 formation of hyaluronic acid coating

Reacting the substrate modified by the polyamine-phenol coating with hyaluronic acid, and specifically comprises the following steps: firstly, the carboxyl of hyaluronic acid is activated, and then the base material with the polyamine-phenol coating is soaked in the reaction solution of hyaluronic acid with the carboxyl activated for reaction for 1-24 h. The carboxyl groups on the hyaluronic acid are in an activated state through an activation reaction, and the reaction of the carboxyl groups on the hyaluronic acid and the amine groups on the base material is promoted.

Further, the activation reaction is to react hyaluronic acid of which the terminal group is carboxyl with 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride (EDC) and N-N-hydroxysuccinimide (NHS), and the activation reaction time is 5-60 min; the molecular weight of hyaluronic acid is 1-10000 KDa. EDC is utilized to enable carboxyl on the hyaluronic acid to be in an activated state, and the grafting amount of the hyaluronic acid on the surface of the base material is further improved by matching with the activation time and the regulation and control of the molecular weight of the hyaluronic acid.

In some preferred embodiments, the activation reaction is performed in 2-morpholinoethanesulfonic acid (MES) buffer; in the mixed solution of the activation reaction, the concentration of 2-morpholine ethanesulfonic acid is 8-12mg/mL, the concentration of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 0.8-1.2mg/mL, the concentration of N-N-hydroxysuccinimide is 0.2-0.3mg/mL, and the concentration of hyaluronic acid is 0.5-50 mg/mL. Hyaluronic acid is introduced more by further regulating and controlling the dosage of each raw material, so that the anti-fouling performance of the material is improved.

The embodiment of the invention provides a material with a biological anti-fouling function, which comprises a substrate, a polyamine-phenol coating formed on the substrate and a hyaluronic acid layer formed on the polyamine-phenol coating; wherein the polyamine-phenol coating is obtained by the reaction of phenolic molecules and polyamine molecules. The hyaluronic acid coating is introduced by utilizing amine groups on the polyamine-phenol coating, and a hydration layer is formed on the surface of the coating after the coating is contacted with an aqueous solution, so that components, cells and the like in blood can be effectively inhibited from being contacted with the coating, the blood compatibility of the material is improved, and the adhesion and proliferation of the cells on the material are effectively reduced.

In some embodiments, the substrate is an inferior vena cava filter or a substrate used to prepare an inferior vena cava filter, among other materials, significantly reducing the risk of surgical failure.

In other embodiments, the functional material can also be used for preparing an artificial heart inner wall anticoagulation surface and an artificial heart-lung machine anticoagulation surface.

The features and properties of the present invention are described in further detail below with reference to examples.

Example 1

The embodiment provides a preparation method of a material with a biological anti-fouling function, which comprises the following steps:

(1) soaking the inferior vena cava filter in Tris (pH value of 8.5) buffer solution containing 1mg/mL dopamine, reacting for 12 hours at room temperature, then ultrasonically cleaning with ultrapure water, then placing the filter into 2.5mg/mL NaOH aqueous solution containing 10 mu g/mL polyallylamine (molecular weight is about 10000Da) and soaking for 6 hours, namely obtaining a layer of wear-resistant coating (marked as PAM DA @ on the surface) with rich amino groups on the surface of the inferior vena cava filter.

(2) MES, EDC, NHS, hyaluronic acid (molecular weight is 1000KDa) and water are mixed to form a 20mL solution and reacted for 20min, wherein the concentrations of MES, EDC, NHS and hyaluronic acid are 10mg/mL, 1mg/mL, 0.24mg/mL and 2mg/mL in sequence. And (2) soaking the inferior vena cava filter coated with the PAM @ DA coating on the surface obtained in the step (1) in the reacted solution for 12 hours to obtain the functional coating of the inferior vena cava filter with the anti-fouling function.

Example 2

(1) the inferior vena cava filter is soaked in a Tris (pH value of 8.5) solution of 0.8mg/mL dopamine, reacts for 12 hours at room temperature, is washed and then is placed into a 2.0mg/mL NaOH aqueous solution containing 8 mu g/mL polyallylamine (molecular weight is about 20000Da) to be soaked for 4 hours, and a dopamine conversion coating (PAM @ DA) which is wear-resistant and rich in amine groups on the surface is obtained on the surface of the inferior vena cava filter.

(2) MES, EDC, NHS, hyaluronic acid (molecular weight 5KDa) and water are mixed to form a 20mL solution and reacted for 10min, wherein the concentrations of MES, EDC, NHS and hyaluronic acid are 8mg/mL, 0.8mg/mL, 0.2mg/mL and 1mg/mL in sequence. And (2) soaking the inferior vena cava filter coated with the PAM @ DA coating on the surface obtained in the step (1) in the reacted solution for 10 hours to obtain the functional coating of the inferior vena cava filter with the anti-adhesion function.

Example 3

(1) soaking the inferior vena cava filter in a Tris (pH value of 9.0) solution of 1.2mg/mL dopamine, reacting for 24 hours at room temperature, then placing the inferior vena cava filter into a 3.0mg/mL NaOH aqueous solution containing 12 mu g/mL PAa (molecular weight of about 100KDa), and soaking for 8 hours to obtain a dopamine conversion coating (PAM @ DA) which is wear-resistant and rich in amine groups on the surface of the inferior vena cava filter.

(2) MES, EDC, NHS, hyaluronic acid (molecular weight 1000KDa) and water are mixed to form a 20mL solution and reacted for 30min, wherein the concentrations of MES, EDC, NHS and hyaluronic acid are 12mg/mL, 1.2mg/mL, 0.3mg/mL and 1.2mg/mL in sequence. Soaking the inferior vena cava filter coated with PAM @ DA coating obtained in the step (1) in the reacted solution for 15 hours to obtain the functional coating of the inferior vena cava filter with the anti-adhesion function.

Example 4

(1) filling the inner cavity of the artificial blood pump with a Tris (pH value of 8.5) buffer solution containing 1mg/mL dopamine, carrying out cyclic reaction at room temperature for 12 hours, washing, then putting the washed artificial blood pump into a 2.5mg/mL NaOH aqueous solution containing 10 mu g/mL polyallylamine (molecular weight is about 10000Da), and soaking for 6 hours, namely obtaining a layer of wear-resistant coating (marked as PAM @ DA) with rich amino groups on the surface of the inferior vena cava filter.

(2) MES, EDC, NHS, hyaluronic acid (molecular weight is 1000KDa) and water are mixed to form a 20mL solution and reacted for 20min, wherein the concentrations of MES, EDC, NHS and hyaluronic acid are 10mg/mL, 1mg/mL, 0.24mg/mL and 2mg/mL in sequence. And (3) filling the inner cavity of the artificial blood pump with the PAM @ DA coating coated on the inner wall surface obtained in the step (1) into the solution obtained after the reaction, and soaking for 12 hours to obtain the functional coating of the inferior vena cava filter with the anti-fouling function.

Test example 1

The material prepared in example 1 was tested for hydrophilic properties and the contact angle before and after HA grafting was tested when the coating was contacted with an aqueous solution, as shown in figure 2.

As can be seen from fig. 2, when the coating was contacted with an aqueous solution, a hydrated layer formed on the surface, decreasing from 82.3 ° ± 3.1 ° before grafting to less than 5 °, demonstrating that the surface appeared to be superhydrophilic.

Test example 2

The material prepared in example 1 was tested for blood compatibility and the results are shown in fig. 3. The test method comprises the following steps: the samples were placed in 24-well plates, 50. mu.L of Platelet Rich Plasma (PRP) was added dropwise to each sample surface, and after PRP was sufficiently spread on the sample surface, incubation was carried out at 37 ℃ for 2 hours. Subsequently, the PRP on the surface of the sample was aspirated and thoroughly rinsed with physiological saline, and rinsedThe washed sample was fixed in 2.5% glutaraldehyde. After the sample was fixed for 12 hours, it was rinsed thoroughly with physiological saline again, and then sequentially at 50% (V)_Ethanol/V_{Distilled water}) 75%, 90%, 100%, 100% ethanol solution, 50% (V)_{Acetic acid isoamyl ester}/V_Ethanol) 75 percent, 90 percent and 100 percent of isoamyl acetate are subjected to gradual dealcoholization. After critical point drying, the surface of the sample is sprayed with gold, and platelet morphology observation is performed under a Scanning Electron Microscope (SEM).

The material prepared in example 1 was tested for cell culture results, which are shown in FIG. 3. The test method comprises the following steps: selecting the density of 5 multiplied by 10⁴cells/cm²Endothelial cells, smooth muscle cells or macrophages are used for seeding the surface of the material. The cells were taken out after culturing for 3 days on the surface of the sample, respectively. After washing with Phosphate Buffered Saline (PBS), the cells were fixed with 2.5% glutaraldehyde for 1 hour. The washed sample was then treated with rhodamine stain for 15 minutes, and finally the morphology of the cells was observed under a fluorescent microscope and recorded by photography.

It can be seen from fig. 3 that the material obtained by the embodiment of the invention effectively inhibits components, cells and the like in blood from contacting with the coating, thereby improving the blood compatibility of the material and effectively reducing the adhesion and proliferation of the cells on the material.

In summary, the present invention provides a material with a bio-anti-fouling function, which is prepared by forming a polyamine-phenol coating on a substrate, wherein the polyamine-phenol coating is formed by reacting a phenolic molecule with a polyamine molecule, and then grafting hyaluronic acid onto the polyamine-phenol coating to form a hyaluronic acid layer, wherein a hydration layer is formed on the surface of the polyamine-phenol coating after the coating contacts with an aqueous solution, such that components and cells in blood can be effectively inhibited from contacting with the coating, thereby improving the blood compatibility of the material, and effectively reducing the adhesion and proliferation of the cells on the material.

The embodiment of the invention also provides a preparation method of the material with the biological anti-fouling function, which comprises the steps of reacting the base material deposited with the phenolic molecular coating with a polyamine molecular solution to form a polyamine-phenol coating on the base material, and grafting hyaluronic acid with an amino group on the polyamine-phenol coating to form a super-hydrophilic coating, so that the functional material is prepared, the inferior vena cava filter can be prepared and formed, and the risk of operation failure is obviously reduced by utilizing the good blood compatibility of the functional material. The functional material can also be used for preparing an anticoagulant surface on the inner wall of an artificial heart and an anticoagulant surface of an artificial heart-lung machine.

The embodiments described above are some, but not all embodiments of the invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the invention as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Claims

1. A material having a biofouling function comprising a substrate, a polyamine-phenol coating layer formed on the substrate, and a hyaluronic acid layer formed on the polyamine-phenol coating layer;

wherein the polyamine-phenol coating is obtained by the reaction of phenolic molecules and polyamine molecules, and the phenolic molecules are catechol or plant polyphenol.

2. The material of claim 1, wherein the phenolic molecules are selected from at least one of catechol, pyrogallol, epicatechin gallate, epigallocatechin gallate, dopamine, norepinephrine, levodopa, dextrodopa, gallic acid and its derivatives, tannic acid, caffeic acid, ferulic acid, 2, 3-dihydroxybenzoic acid, and 3, 4-dihydroxybenzoic acid;

preferably, the phenolic molecules are dopamine and norepinephrine.

3. The material with biological antifouling function as claimed in claim 1, wherein the polyamine-based molecule is at least one selected from polyallylamine, polyvinylamine, polylysine and chitosan;

preferably, the polyamine-based molecule is polyallylamine;

preferably, the base material is at least one of medical stainless steel, cobalt alloy, nickel-titanium alloy, titanium and medical titanium alloy;

preferably, the base material is a medical polymer material.

4. A process for the preparation of a material with a biofouling functionality according to any one of claims 1 to 3, comprising: reacting the substrate on which the phenolic molecule coating layer is deposited with a polyamine molecule solution to form a polyamine-phenolic coating layer on the substrate; grafting hyaluronic acid on the polyamine-phenolic coating.

5. The preparation method according to claim 4, wherein the reaction of the substrate deposited with the phenolic molecular coating and the polyamine molecular solution is carried out by soaking the substrate deposited with the polydopamine coating in the polyamine molecular solution for 0.1-24 h;

preferably, the reaction time is 4-8 h;

preferably, the polyamine molecular solution is a mixed solution of polyallylamine, strong base and solvent, and the pH value of the polyamine molecular solution is greater than 7;

more preferably, the pH value of the polyamine molecular solution is 11-14;

preferably, the strong base is sodium hydroxide, and the concentration of the sodium hydroxide in the polyamine molecular solution is 0.1-10 mg/mL;

more preferably, the concentration of the sodium hydroxide in the polyamine molecular solution is 2-3 mg/mL;

preferably, the polyamine molecule polyallylamine has a molecular weight of 1000-1000000;

preferably, the concentration of the polyallylamine in the polyamine molecular solution is 0.1-50 mug/mL;

more preferably, the concentration of polyallylamine in the polyamine-based molecular solution is 2.5-20. mu.g/mL.

6. The method of claim 5, wherein the substrate having the polyamine-phenolic coating deposited thereon is prepared by a process comprising: soaking the base material in an alkaline solution containing catechol monomer, and reacting for 1-24 h;

preferably, the pH value of the alkaline buffer solution containing the catechol monomer is 7-9;

preferably, the catechol monomer is dopamine, and the dosage of the dopamine is 0.25-2 mg/mL.

7. The method of claim 5, wherein the step of grafting hyaluronic acid onto the polyamine-phenolic coating comprises the steps of: firstly, activating hyaluronic acid, and then soaking the base material modified by the polyamine-phenol coating in a mixed solution of hyaluronic acid after activation for grafting for 1-24 h;

preferably, the hyaluronic acid is subjected to an activation reaction by reacting hyaluronic acid with 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride and N-N-hydroxysuccinimide;

preferably, the activation reaction time is 5-60 min;

preferably, the molecular weight of the hyaluronic acid is 1-10000 KDa;

preferably, the activation reaction is carried out in 2-morpholinoethanesulfonic acid buffer;

preferably, in the mixed solution of the activation reaction, the concentration of 2-morpholinoethanesulfonic acid is 8 to 12mg/mL, the concentration of 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide hydrochloride is 0.8 to 1.2mg/mL, the concentration of N-N-hydroxysuccinimide is 0.2 to 0.3mg/mL, and the concentration of hyaluronic acid is 0.5 to 50 mg/mL.

8. Use of a material having a biofouling functionality according to any one of claims 1 to 3 or of a functional material prepared by the preparation process according to any one of claims 4 to 7 for the preparation of a recoverable inferior vena cava filter.

9. Use of the material with biological anti-fouling function as defined in any one of claims 1-3 or the functional material prepared by the preparation method as defined in any one of claims 4-7 in preparation of an artificial heart inner wall anticoagulation surface.

10. Use of the material with biological anti-fouling function of any one of claims 1-3 or the functional material prepared by the preparation method of any one of claims 4-7 in the preparation of an artificial heart-lung machine anticoagulant surface.